Arthritis & Rheumatism, Volume 62, November 2010 Abstract Supplement

Abstracts of the American College of Rheumatology/Association of Rheumatology Health Professionals Annual Scientific MeetingAtlanta, Georgia November 6-11, 2010.

ALD518 (BMS945429), a High-Affinity Anti-Interleukin-6 Monoclonal Antibody, Provides Improvements in Health-Related Quality of Life (HRQoL) in Patients with Rheumatoid Arthritis (RA) and an Inadequate Response to Methotrexate.

Background:

ALD518 (BMS945429) is a monoclonal antibody directed against IL-6. Rapid and significant ACR responses have previously been demonstrated with ALD518 in patients with RA through 16 weeks1. Here, the authors report HRQoL outcomes from a Phase II randomized controlled trial of intravenous ALD518 in patients with active RA and inadequate responses to methotrexate (MTX).

Methods:

This was a 16-week, double-blind, placebo (PL)-controlled study in which patients with active RA were randomized 1:1:1:1 to ALD518 80, 160 or 320 mg or PL. Two infusions were given (at Day 1 and Week 8), and patients were maintained on stable doses of MTX (>=10 mg/week) throughout. HRQoL was evaluated by the Medical Outcomes Survey Short Form-36 (SF-36). Analyses were performed on the modified intent-to-treat population for patients with data available at the visit of interest (as observed). Minimum clinically important differences (MCID) were 2.55.0 for physical and mental component summary scores (PCS and MCS, respectively); 5.010.0 for domain scores and MID for SF-6D=0.0412,3.

Results:

127 patients were randomized and treated, and 116 completed the trial (80 mg, 29/32; 160 mg, 33/34; 320 mg, 25/28; PL, 29/33); mean age was 52.3 years; mean RA duration was 6.8 years; and mean tender and swollen joint counts were 26.1 and 16.7, respectively. Mean baseline PCS and MCS were 31.0 and 35.0, 2 and 1.5 standard deviations less than normative values of 50, respectively. At Week 12, improvements in PCS and MCS were 7.1 and 12.3 in the 80 mg group, 6.1 and 7.6 in the 160 mg group and 8.5 and 13.5 in the 320 mg group versus 4.2 and 1.8 in the PL group. At Week 16, in the ALD518 80, 160 and 320 mg groups, respectively, improvements in PCS were 6.7, 6.6 and 8.3 versus 4.7 with PL; improvements in MCS were 10.8, 9.4 and 11.0, respectively, versus 3.8 for PL. Improvements at Week 16 in MCS scores were observed to be greater in the ALD518 80 and 320 mg groups (p=0.05 each) when compared with PL, and >=MCID. Observed mean changes from BL in bodily pain, general health and social functioning in the ALD518 80,160 and 320 mg groups exceeded those with PL; and in vitality in the 160 and 360 mg groups and mental health in 360 mg group. Changes >=MCID were observed in all domains, including SF-6D (Table).

Domain* (+ age/gender norm)

Time point

ALD518 80 mg (n = 32)

ALD518 160 mg (n = 33)

ALD518 320 mg (n = 29)

Placebo - (n = 32)

Physical functioning

Baseline score

41.6

49.7

43.8

42.4

(79.6)

Mean change to Wk 16

15.2

14.8

20.0

13.9

Role physical (80.1)

Baseline score

29.9

30.7

32.5

33.5

Mean change to Wk 16

18.8

22.0

24.6

14.8

Bodily pain (68.3)

Baseline score

25.3

28.6

29.1

29.2

Mean change to Wk 16

22.3

23.0

26.3

10.0

General health

Baseline score

35.6

37.2

38.0

37.6

(69.5)

Mean change to Wk 16

9.5

10.1

10.1

3.0

Vitality (58.2)

Baseline score

32.2

32.8

36.6

40.2

Mean change to Wk 16

14.5

20.1

19.8

6.4

Social functioning

Baseline score

39.1

40.2

44.8

45.5

(83.6)

Mean change to Wk 16

24.6

26.5

23.7

7.2

Role emotional

Baseline score

39.1

46.2

38.8

42.9

(86.8)

Mean change to Wk 16

20.1

15.2

21.0

11.6

Mental health (74.9)

Baseline score

44.1

49.1

42.9

51.1

Mean change to Wk 16

12.6

15.5

20.9

5.2

SF-6D (0.831)

Baseline score

0.556

0.584

0.579

0.592

Mean change to Wk 16

0.140

0.150

0.170

0.070

*0100 scores are presented for each domain to enable interpretation within the context of the MCIDs; shading indicates changes >=MCID in domain scores and >=MID in SF-6D; p < 0.05

Conclusions:

Treatment over 16 weeks with the IL-6 inhibitor ALD518 resulted in improvements in physical, mental and emotional aspects of HRQoL that were clinically meaningful. These improvements were statistically significant in some but not all SF-36 domains, which may be due to large changes in the placebo group. These data support continued evaluation of ALD518 for treatment of patients with active RA and inadequate responses to MTX.